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Reducing the amount of dietary fat and empty calories may improve memory and help reduce the negative effects of stress and aging on thinking and learning, recent animal studies suggest. Other work shows that diets high in fats and carbohydrates may worsen cognitive losses due to sleep apnea in those prone to the condition.

Nearly two-thirds of adults in the United States are overweight, and 30.5 percent are obese, according to data from a recent National Health and Nutrition Examination Survey.

“We are in the midst of an obesity epidemic in the United States,” says Barry Levin, MD, of the VA Medical Center in East Orange, N.J. “These new studies show that diets high in fat are a risk factor for not only heart disease, hypertension, and diabetes, but for cognitive decline as well.”

Veerendra Kumar Madala Halagappa, PhD, and Mark Mattson, PhD, of the National Institute on Aging studied how a diet high in fat and sugar affected learning and memory in mice.

Young adult male mice were divided into four groups by diet: normal (control) diet, high-saturated-fat diet, high-sugar diet, and diet high in saturated fats and sugar. They were kept on the diet for four months. Mice on the high-fat diet or the diet high in both fats and sugar had gained significantly more weight than those on the control and high sugar diets after the four months.

To test their learning and memory, the mice then completed a maze task. Halagappa found that the mice on the high-fat and high-fat, high-sugar diets could not learn and remember the maze as well as those on the other diets.

“These results provide direct evidence that fast food diets, particularly a diet high in saturated fats, can have an adverse effect on learning and memory,” he says.

Halagappa and Mattson took the work a step further to find out how a high-fat diet might affect the response of nerve cells involved in learning and memory to stress. They designed an experiment in which mice that had been on the four different diets were exposed to a neurotoxin called kainic acid, which is known to damage nerve cells in the hippocampus, a brain region involved in learning and memory. When mice on the control diet or the high-sugar diet were exposed to kainic acid, their learning and memory were somewhat impaired. In contrast, the memory of mice on the high-fat and high-fat, high-sugar diets was severely impaired by the neurotoxin.

“These findings show that fast food diets impaired memory acquisition in mice and made their brains more vulnerable to kainate-induced cognitive dysfunction,” says Halagappa. “If such diets have similar effects in humans, then reducing the amount of fat and empty calories may improve one's memory and increase resistance to age- and stress-related cognitive impairment.”

In other work supporting the notion that a high-fat diet can result in impaired learning and memory, John Morley, MD, and his colleagues Susan Farr, PhD, and William Banks, PhD, in the division of geriatric medicine at the VA Medical Center in St. Louis compared obese CD-1 mice with normal-weight CD-1 mice in learning and memory of a T-maze footshock avoidance test and a lever press memory test.

Obese mice were fed a diet containing about 10 percent fat for seven months, while control mice were fed standard lab chow containing only 5 percent fat. At eight months of age, the mice on the high-fat diet weighed about 60 percent more than the mice on the regular diet.

The mice were trained to avoid a shock to their feet in a T maze until they successfully avoided one shock. One week later, they were tested for how well they retained a memory of the foot shock by continuing their training until they avoided the shock five times in six consecutive trials. The obese mice took significantly more trials than the normal-weight mice to both acquire and retain a memory of the foot shock.

The mice were also trained to press a lever in order to receive a drink of milk as reinforcement. They were trained every other day (Monday, Wednesday, and Friday) for two weeks. The obese mice required significantly more trials than control mice to learn to press a lever for milk reinforcement.

“We conclude from these studies that obesity causes a decline in the ability to acquire new facts and to remember them,” Morley says.

Ann-Charlotte Granholm, PhD, DDS, and her colleagues at the Medical University of South Carolina in Charleston explored whether a diet high in cholesterol and hydrogenated fats affected working memory in middle-aged rats (corresponding to 60 and older for humans).

Rats on the high-fat, high-cholesterol diet had significantly higher plasma triglycerides, total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol compared with controls. Weight increase and food consumption were similar between the groups. This ruled out the effects of weight gain on any effects seen in the rats on the high-fat diet.

During their final two weeks on the diet, the rats were tested in a water version of the radial arm maze, which tests the animals' working memory (for items that are changed during the test) as well as their reference memory (for items that did not change during the test). Animals on the high-fat regimen made more errors than animals fed the control diet, especially during the trial that placed the highest demand on their working memory.

“This shows that animals given a high-fat diet were less able to maintain successful performance when working memory load was the highest,” Granholm says.

Diets high in fat and carbohydrates may also worsen cognitive losses due to sleep apnea in those who are prone to the condition, according to work done in rats.

Researchers at Kosair Children's Hospital Research Institute in Louisville , Kentucky , found that a diet high in fats and carbohydrates worsened cognitive deficits in rats exposed to repeated brief periods of low oxygen during sleep.

In the work by David Gozal, MD, and his colleagues, adult male rats were fed either a diet high in fats and refined carbohydrates or a diet low in fats and high in complex carbohydrates starting at postnatal day 30 and continuing for 90 days. They were then exposed to either normal levels of oxygen or brief periods of low oxygen (intermittent hypoxia) for 12 hours a day for 14 days.

The investigators then measured levels of CREB phosphorylation, a measure of cellular tolerance to stress and of the ability to generate memory under situations of hypoxia, in different brain region. Rats in the normal oxygen group that ate a diet low in fats but high in complex carbohydrates showed normal levels of CREB phosphorylation in the hippocampus, a part of the brain involved in learning and memory. Rats in three other groups—intermittent hypoxia alone; high fat, refined carbohydrate diet; and intermittent hypoxia with high-fat, refined carbohydrate diet—showed substantial decreases in CREB phosphorylation.

Rats in the intermittent hypoxia and the high fat, refined carbohydrate diet groups also had much more difficulty on a memory task than did rats exposed to intermittent hypoxia alone or fed the high fat, refined carbohydrate diet alone.

“Our new findings provide the first support for the hypothesis that diet can modify an individual's vulnerability to cognitive impairments caused by these brief periods of low oxygen concentrations such as encountered in patients with sleep apnea,” says Gozal. “These results suggest that an improved diet can be an important part of the treatment regimen in patients with sleep apnea.”

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